A proof-of-concept model for the identification of the key events in the infection process with specific reference to Pseudomonas aeruginosa in corneal infections (original) (raw)
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Pseudomonas aeruginosa host-pathogen interactions in human corneal infection models
Journal of EuCornea
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Phenotype of Pseudomonas aeruginosa Isolates Causing Corneal Infection Between 1997 and 2000
Cornea, 2003
Purpose. To investigate the relationship between functional phenotype of Pseudomonas aeruginosa and the associated human corneal infection. Methods. This was an experimental pilot study of patients presenting with corneal infections at the Jules Stein Eye Institute with presumed P. aeruginosa infection during the period from 12/30/97 to 9/1/00. Thirteen patients were admitted to the study based on positive identification of the causative pathogen as P. aeruginosa and patient consent. Data were collected (including bacterial cultures, lens wear schedule and care, gender and age, completed history questionnaire, clinical photographs). Statistical analysis of possible correlations was performed. Phenotypes of P. aeruginosa were determined, and clinical factors associated with infection were explored. Results. Both invasive and cytotoxic phenotypes of P. aeruginosa were isolated in equal proportion. Cytotoxic strains and invasive strains were found to be associated with patients younger than 50 years of age and older than 50 years of age, respectively. Conclusions. P. aeruginosa remains a significant pathogen in corneal infection, especially during contact lens wear. The age of the patient may influence the phenotype of P. aeruginosa causing infection. Since invasive and cytotoxic strains have different effects on corneal cells, treatment of the infection might require different approaches depending on this phenotype of the causative bacteria.
Modeling of bacterial keratitis of Pseudomonas aeruginosa etiology in the experimental model
2021
Background: Pseudomonas aeruginosa keratitis demonstrates an aggressive course, high resistance to antimicrobial therapy, and it also leads to a significant reduction of visual acuity. The purpose of our study was to develop an experimental model of Pseudomonas aeruginosa keratitis and investigate clinical features of corneal lesions in rabbits. Material and methods: A total of 32 rabbits were divided randomly into three groups. The animals of the experimental group 1 (8 rabbits) underwent scarification of the cornea and instillation of archival strain suspension of P. aeruginosa into the conjunctival sac. In group 2 (12 rabbits), corneal de-epithelialization followed by instillation of microbial suspension was performed. In animals of group 3 (12 rabbits), after the de-epithelialization followed by instillation of one-day suspension of the pathogen, the cornea’s surface was covered with a sterile soft contact lens for 16–24 hours. In half of the animals (6 rabbits), the contact len...
Pseudomonas aeruginosa invades corneal epithelial cells during experimental infection
Infection and immunity, 1994
Pseudomonas aeruginosa is considered an extracellular pathogen. Using assays to determine intracellular survival in the presence of gentamicin, we have demonstrated that some strains of P. aeruginosa are able to invade corneal cells during experimental bacterial keratitis in mice. Although intracellular bacteria were detectable 15 min after inoculation, the number of intracellular bacteria increased in a time-dependent manner over a 24-h period. Levels of invasion were similar when bacteria were grown as a biofilm on solid medium and when they were grown in suspension. Intracellular bacteria survived in vitro for at least 24 h, although only minimal bacterial multiplication within cells was observed. P. aeruginosa PAK and Escherichia coli HB101 did not cause disease in this model and were not isolated from corneas after 24 h even when an inoculum of 10(8) CFU was applied. Transmission electron microscopy of corneal epithelium from eyes infected for 8 h revealed that intracellular ba...
Why Does the Healthy Cornea Resist Pseudomonas aeruginosa Infection?
American Journal of Ophthalmology, 2013
Purpose-To provide our perspective on why the cornea is resistant to infection based on our research results with Pseudomonas aeruginosa. Perspective-We focus on our current understanding of the interplay between bacteria, tear fluid and the corneal epithelium that determine health as the usual outcome, and propose a theoretical model for how contact lens wear might change those interactions to enable susceptibility to P. aeruginosa infection. Methods-Use of "null-infection" in vivo models, cultured human corneal epithelial cells, contact lens-wearing animal models, and bacterial genetics help to elucidate mechanisms by which P. aeruginosa survive at the ocular surface, adheres, and traverses multilayered corneal epithelia. These models also help elucidate the molecular mechanisms of corneal epithelial innate defense. Results and Discussion-Tear fluid and the corneal epithelium combine to make a formidable defense against P. aeruginosa infection of the cornea. Part of that defense involves the expression of antimicrobials such as β-defensins, the cathelicidin LL-37, cytokeratin-derived antimicrobial peptides, and RNase7. Immunomodulators such as SP-D and ST2 also contribute. Innate defenses of the cornea depend in part on MyD88, a key adaptor protein of TLR and IL-1R signaling, but the basal lamina represents the final barrier to bacterial penetration. Overcoming these defenses involves P. aeruginosa adaptation, expression of the type three secretion system, proteases, and P. aeruginosa biofilm formation on contact lenses. Conclusion-After more than two decades of research focused on understanding how contact lens wear predisposes to P. aeruginosa infection, our working hypothesis places blame for microbial keratitis on bacterial adaptation to ocular surface defenses, combined with changes to the biochemistry of the corneal surface caused by trapping bacteria and tear fluid against the cornea under the lens.
Journal of Medical Microbiology, 2008
Pseudomonas aeruginosa is one of the common pathogens associated with corneal infection, particularly in contact lens-related keratitis events. The pathogenesis of P. aeruginosa in keratitis is attributed to the production of virulence factors under certain environmental conditions. The aim of this study was to determine differences in the virulence factors of P. aeruginosa isolated from contact lens- and non-contact lens-related keratitis. Associations were assessed between type III secretion toxin-encoding genes, protease profiles, biofilm formation, serotypes and antibiotic-resistance patterns among 27 non-contact lens- and 28 contact lens-related P. aeruginosa keratitis isolates from Australia. Strains with a exoS +/exoU − genotype and a type I protease profile predominated in the non-contact lens-related keratitis isolates, whereas the exoS −/exoU + and a type II protease profile was associated with contact lens-related isolates (P<0.05). A strong biofilm formation phenotype...
Extended contact lens wear enhances Pseudomonas aeruginosa adherence to human corneal epithelium
Investigative ophthalmology & visual science, 1992
Extended wear of soft contact lenses is associated with an increased risk of Pseudomonas aeruginosa infection of the cornea. To assess the role of bacterial adherence in the pathogenesis of these infections, superficial corneal epithelial cells and leukocytes from ten patients who use extended-wear soft lenses and ten control eyes were compared for their propensity to attach P. aeruginosa in vitro. Cells were washed from the cornea by saline irrigation, incubated with a 10-ml solution containing 10(7) colony-forming units/ml of bacteria at 35 degrees C for 30 min, collected on a filter, and prepared using a modified acridine orange staining method. Fluorescence microscopy showed bacterial adherence to corneal epithelial cells, leukocytes, and ocular mucus. The mean number of bacteria adhering to epithelial cells was 2.6 for control eyes and 6.6 for the lens-wearing eyes (P = 0.002). The percentage of epithelial cells attaching greater than or equal to four bacteria was higher for le...
Epidemiology of Pseudomonas aeruginosa keratitis in contact lens wearers
Epidemiology and Infection, 1995
This study evaluated the epidemiology of Pseudomonas aeruginosa keratitis in contact lens (CL) wearers; the relationships between CL storage case contamination and CL hygiene practice and between CL hygiene and the development of keratitis. Sixteen CL wearers with keratitis were compared with 44 asymptomatic controls. Lens hygiene practice was assessed and CL care materials, domestic water sites and endogenous sites were evaluated microbiologically. Poor CL hygiene was not associated with Ps. aeruginosa keratitis. There was an association between keratitis and bacterial contamination of the CL and storage case (P < 00005). Lens and storage case contamination were not significantly associated with poor hygiene. No domestic or endogenous source for Ps. aeruginosa was found. Causative organisms may be derived from other sources, but CLs and CL storage cases provide a favourable environment for Ps. aeruginosa colonization. Changing the CL care environment to one less favourable for Ps. aeruginosa may help to eliminate this problem.